The radio partnership is aimed at driving donations to BHF shops, and has been brokered by Omnicom agencies PHD and Drum.
In a series of conversations, the stations' DJs will chat to local people who have survived a heart attack or been affected by a loved one experiencing a heart attack. They will also interview researchers from the British Heart Foundation.
Listeners will be encouraged to donate unwanted clothes, shoes, toys, books and CDs to BHF shops in the campaign, which will run on 33 regional stations until the end of September.
The Great British Bag-athon supports the BHF’s new brand positioning, called "Fight for every heartbeat", which launched in February.
On-air will be supported by community activities, including awarding listeners, activity from local businesses, broadcasts from big donator locations such as local schools or offices and on-site street team activity at BHF shops.
Jessica Crawford, media manager at PHD, said they chose a radio partnership over a traditional above-the-line campaign to, "create a sense of national momentum and to leverage the influence that radio stations have in their local communities."
She added: "The fact that all three large radio houses have got involved just goes to show the importance of the work the British Heart Foundation do."
Nick Radmore, head of social marketing and brand at the British Heart Foundation, said: "We're excited to be working with the three biggest radio groups in the UK to bring together this innovative campaign.
"This radio partnership provides us with the opportunity to show how heart disease can affect anyone, and how everyone can join the fight against the UK’s single biggest killer by simply having a clear-out and taking it to their local BHF shop."
Coronary heart disease is the UK’s single biggest killer, according to BHF.
PHD and Drum’s work with the charity included a tie-up with ITV's Coronation Street when the show’s script featured character Audrey suffering a heart attack last year.
BHF ran ads in commercial breaks and used images of Audrey in in-store marketing.